SELECTIN BINDING GLYCOPEPTIDES

Abstract: Glyco-amino acids or glycopeptides that have three-dimensionally stable configuration for the presentation of functional groups, fucose, or an analogue or derivative thereof, covalently linked to an amino acid or peptide with a free carboxylic acid group, that facilitate binding between those groups and receptors on selectins, represented by general structural formula (I) as shown in claim 1. The glycopeptides of structural formula (I) can be administered to a subject to treat inflammation.

Description: SELECTTN BINDING GLYCOPEPTIDES Field of the Invention This invention relates generally to medicinal chemistry, and preferably to methods of synthesizing and identifying medically useful glyco-amino acids or glycopeptides which are characterized by their capacity to bind to one or more selectins (E-, L-, and P-selectins). Background of the Invention Carbohydrate-protein interactions form the basis of a host of biological processes (Clarke A. E. & Wilson I. A., eds. (1988), Carbohvdrate-protein interactions (Springer, Heidelberg); and Liener et al (1986) The Lectins: Properties. Functions and Applications in Biology and Medicine (Academia, Orlando, FL) ). The role of carbohydrates in physiologically relevant recognition has been widely considered (Brandley et al., J Leuk Biol (1986) 40:97; and Sharon et al., Science (1989) 246:227). For example, the cell-surface mediates such processes as cell-cell adhesion (Springer et al, Nature (1990) 346:425) and lymphocyte adhesion through lymphoid tissues (Stoolman, L. M., Cell (1986) 5_ϋ: 907). Carbohydrate recognition is central to the enzymatic synthesis and degradation of polysaccharides, glycoproteins and glycolipids that play essential roles in metabolism and maintenance of cellular structures. Tumor associated glycolipids have been reported in fetal tissue and a variety of human cancers, including CML cells (Fukuda et al., J Biol Chem (1986) 261:2376: Magnani et al., J Biol Chem (1982) 257:14365; Hakomori et al., Biochem Biophv Res Comm (1983) 113:791). This has led to the hypothesis that these structures may be important in many developmental and oncogenic processes (Magnani et al., J Biol Chem (1982) 257: 14365). Smaller quantities of most of these carbohydrates can be found in normal human tissue (see Fukushi et al., J Exp Med (1984) 160:506). but until now no function for these structures has been reported. Adhesion of circulating neutrophils to stimulated vascular endothelium is a primary event of the inflammatory response. Several receptors have been implicated in this interaction, including a family of putative lectins that includes L-selectin (gp90 MEL , Leu8), P-selectin (GMP-140, PADGEM) and E-selectin (ELAM-1) (Gong et al., Nature (1990) 343:757; Johnston et al., Cell (1989) 56:1033; Geoffrey et al., J Cell Biol (1989) IQ9:2463; Lasky et al., £eU (1989) 56:1045). These receptors each contain a domain with sequence homology to calcium dependent lectins. The receptor gp9()MEL has been demonstrated to recognize a carbohydrate (See Geoffrey et al., J Cell Biol (1989) 109:2463). Endogenous ligands for these receptors are beginning to be characterized (see U.S. Patent 5,143,712 issued Sept 1, 1992, incorporated herein by reference). E-selectin or ELAM-1 is particularly interesting because of its transient expression on endothelial cells in response to IL-1 or TNF (Bevilacqua et al., Science (1989) 243:1160). The time course of this induced expression (2-8 h) suggests a role for this receptor in initial neutrophil extravasation in response to infection and injury. Furthermore, Bevilacqua et al (Bevilacqua et al., Proc Natl Acad Sci USA (1987) £4-9238) have demonstrated that human neutrophils or HL-60 cells will adhere to COS cells transfected with a plasmid containing a cDNA encoding for the ELAM-1 receptor. Several different groups have published papers regarding ELAM-1 ligands which ligands are also referred to as LECAM-2 ligands. Lowe et al (1990) demonstrated a positive correlation between the LECAM-2 dependent adhesion of HL- 60 cell variants and transfected cell lines, with their expression of the sialyl Lewis x (sLe χ ) oligosaccharide, Neu NAc α2-3Gal-βl-4(Fuc αl-3)-GlcNAc. They concluded that one or more members of a family of oligosaccharides consisting of sialylated, fucosylated, lactosaminoglycans are the ligands for the lectin domain of LECAM-2. Phillips et al (1990) used antibodies with reported specificity for sLe to inhibit the LECAM-2 dependent adhesion of HL-60 or LEC 11 CHO cells to activated endothelial cells. Liposomes containing difucosylated glycolipids with terminal sLe x structures inhibited adhesion, while those containing nonsialylated Le χ structures were partially inhibitory. Walz et al (1990) were able to inhibit the binding of a LECAM-2-lgG chimera to HL-60 cells with a monoclonal antibody directed against sLe χ or by glycoproteins with the sLe* structure, but could not demonstrate inhibition with CD65 or CD 15 antibodies. Both groups concluded that the sLe structure is the ligand for LECAM-2. P-selectin expressed on activated platelets mediates binding to multiple leukocyte types ( Bevilacqua et al, J. Clin. Inve.st. (1993) 9.1:379). Endothelial P- selectin also supports leukocyte adhesion. LECAM-1 is particularly interesting because of its ability to block neutrophil influx (Watson et al., Nature (1991) 249:164-167). It was expressed in chronic lymphocytic leukemia cells which bind to HEV (see Spertini et al., Nature (1991) 249_:691-694). It is believed that HEV structures at sites of chronic inflammation are associated with the symptoms of disease such as rheumatoid arthritis, psoriasis, and multiple sclerosis. Information regarding the DNA sequences encoding endothelial cell-leukocyte adhesion molecules are disclosed in PCT published application WO90/13300 pubUshed November 15, 1990 incorporated herein by reference. The PCT publication cites numerous articles which may be related to endothelial cell-leukocyte adhesion molecules. The PCT publication claims methods of identifying ELAM-ligands, as well . as methods of inhibiting adhesion between leukocytes and endothelial cells using such ligands and specifically refers to MILAs which are described as molecules involved in leukocyte adhesion to endothelial cells. In general, the above publications are directed toward identifying and characterizing endogenous ligands which are carbohydrates. The development of potent inhibitors of carbohydrate-specific proteins would be of considerable importance in the generation of new therapeutic agents. Oligosaccharides are well positioned to act as recognition molecules due to their cell surface location and structural diversity. However, these carbohydrates are very complex in nature and are expensive and time consuming to synthesize. Chemical synthesis of oligosaccharides requires sophisticated strategies that control product stereochemistry and regiochemistry. Enzymatic synthesis using glycosyltransferases, a viable alternative to chemical synthesis, is limited by the availability of enzymes with appropriate specificities. Peptides have been suggested as an alternative approach to the synthesis of polysaccharide ligands for carbohydrate-specific receptors (Oldenburg et al, Proc. Natl. Acad. Sci. (1992) ≤9:5393). Cell-specific glycopeptide ligands coupled to bioactive materials have been used as a means to deliver said bioactive materials to the selected site (see European Patent Application, Publication No. 63373, published October 27, 1982; and U.S. Patent 4,386,026 issued May 31, 1983 incorporated herein by reference). Summary of the Invention A primary object of the invention is to provide medically useful glyco-amino acids or glycopeptides (herein also referred to as compounds) that are characterized by their capacity to bind to certain selectins, and that are cost-effective to synthesize. A second object of the invention is the description of certain glyco-amino acids or glycopeptides that bind to certain selectins, that is have selectin ligand activity, and consist of fucose, or an analogue or derivative thereof, attached to an amino acid or a peptide having a free carboxylic acid group. Relative to sLe χ , a known selectin ligand, the invention glyco-amino acids or glycopeptides are cost-effective to synthesize. A third object of the present invention is a description of the design and synthesis of glyco-amino acids or glycopeptides that have three-dimensionally stable configurations for the presentation of certain functional groups, a charged group, preferably a carboxylic acid or a sulfate group, and fucose, or analogues or derivatives thereof, such that fucose is covalently linked to an amino acid or a peptide with a free carboxylic acid group, and such that the orientation of the functional groups facilitate binding between those groups and certain selectins. Such invention glyco-amino acids or glycopeptides are represented by the following general structural formula I: wherein m and u are integers of from 1 or 2; p, q and w are integers of from 1 to 6; r and s are integers of from 0 or 1; and t is an integer of from 0 to 3; and A is -COOH or -CH 2 OSO 3 H; B is -Ri, -CH(Ri) 2 , -CH 2 OCH 2 Ri 0 r -CH 2 SCH 2 Ri; D is -Li-[(CH 2 ) w -M] r or -L2-[(CH 2 ) W -M] r ; E is H or -(CH 2 ) w -[K-(CH 2 ) q ] r -Mi with the proviso that either G is H or M2 is H, when E is -(CH 2 ) w -[K-(CH 2 ) q ] r -Mi ; G is H or -[K-(CH 2 ) q ] r -M 2 with the proviso that either E is H or M- is H when G is -[K-(CH 2 ) q ] r -M2 ; J is -SO 2 - when D is -Li-[(CH 2 ) W -M] r ; or J is -CO- or -CS- when D is -L2-[(CH 2 ) W -M] r ; K is -O-, -S-, -NH-, -S-S-, -CO-, -CONH- ; Li is -NH-, -CH 2 -, -NHR or -R4 with the proviso that Li is either R4 or -NHRi when r is 0; L is -O-, -S-, -NH-, -CH 2 -, -OR4, -SR4 , -NHRi 0 r -R4 with the proviso that L2 is either -OR4, -SR4 , -NHR or -R4 when r is 0 ; M, Mi and M2 are independently H or -[CO-Q] s Q is a carrier moiety to obtain multivalent compounds, the carrier moieties selected from the group of amines such as -N(CH 2 CH 2 NH-) 3 , proteins and peptides; X is -R2, -OR2 or -CH 2 OR2; Y is -(CHR3) t - with the proviso that there are no more than two OH groups; or -O-(CHR3) u - with the proviso that there is no more than one OH group ; wherein R 1 and R 2 are independently H, an alkyl group containing 1 to 6 carbon atoms, aryl g group or an arylalkyl group; R 3 is H or OH; R4 is an alkyl group containing 1 to 6 carbon atoms, aryl group or an arylalkyl group. Zis (d): The glyco-amino acids or glycopeptides may be in the form of a prodrug or in the form of multivalent derivatives of compounds of structural formula I. A fourth object of the invention is to provide a description of methods to treat or diagnose disease using glyco-amino acids or glycopeptides. A fifth object of the invention is to provide a composition comprising a glyco- amino acid or glycopeptide of the current invention bound to a detectable label and/or bound to a pharmaceutically active drug such as an anti-inflammatory drug. A sixth object of the invention is to provide a pharmaceutical formulation containing a glyco-amino acid or glycopeptide of the current invention which is useful for treating or diagnosing certain diseases. A seventh object of the invention is to provide a pharmaceutical formulation containing a glyco-amino acid or glycopeptide of the invention which is useful for treating inflammation. An eighth object of the invention includes providing methods to treat inflammation and to determine the site of inflammation by administering formulations of the type referred to above. Another object is to provide a pharmaceutical formulation containing a glyco- amino acid or glycopeptide of the current invention which is useful for treating cancer. These and other objects, advantages and features of the present invention will become apparent to those persons skilled in the art upon reading the details of the isolation, structure, formulation and usage as more fully set forth below, references being made to the accompanying figures and general structural formulae forming a part hereof wherein like symbols refer to like molecular moieties throughout. Brief Description of the Drawings This invention may be better understood and its numerous objects, advantages and features will become apparent to those skilled in the art by reference to the accompanying figures as follows: Figure 1 is a cross-sectional schematic view showing the interaction between white blood cells and activated endothelial cells. Figure 2 is a cross-sectional schematic view showing how glyco-amino acids or glycopeptides of the invention might be used as pharmaceuticals to block ELAM-1. Figure 3 is a cross-sectional schematic view showing how glyco-amino acids or glycopeptides of the invention might be used as pharmaceuticals to block LECAM-1. Figure 4 is a graph that shows that N-[(l-deoxy-α-L-fucopyranosyl) acetyl]-L- proline-L-phenylalanine (#l), N-[(l-deoxy-α-L-fucopyranosyl)acetyl]-L-alanine-L- proline-L-phenylalanine (#2), N-ω-t-butoxylcarbonyl-.V-α-[(l-deoxy-α-L- fucopyranosyl) acetyl]-L-lysine (#3), N-[4-(l-deoxy-α-L-fucopyranosyl)n-butanoyl]- L-proline-L-phenylalanine (#4), N-[(l-deoxy-α-L-fucopyranosyl) acetyl]-L-proline-L- phenylglycine (#5), and N-[4-(l-deoxy-α-L-fucopyranosyl)n-butanoyl]-L- phenylalanine (#6) inhibit the binding of sLe x to L-selectin. The compounds were tested at several concentrations, and the results are expressed as percent of control binding. Figure 5 is a graph that show thatN-[(l-deoxy-α-L-fucopyranosyl)acetyl]-L- proline-L-phenylalanine (#1), N N-ω-t-butoxylcarbonyl-N-α-[(l-deoxy-α-L- fucopyranosyl) acetyl]-L-lysine (#3), N-[4-(l-deoxy-α-L-fucopyranosyl)n-butanoyl]- L-proline-L-phenylalanine (#4), and N-[(l-deoxy-α-L-fucopyranosyl) acetyl]-L- prohne-L-phenylglycine (#5) inhibit the binding of sLe χ to P-selectin. The compounds were tested at several concentrations, and the results are expressed as percent of control binding. Figure 6 has graphs showing the ability of N-[(l-deoxy-α-L-fucopyranosyl) acetyl]-L-proline-L-phenylalanine (#1), and N-[(l-deoxy-α-L-fucopyranosyl) acetyl]- L-alanine-L-proline-L-phenylalanine (#2) to inhibit the binding of sLe χ to P-selectin in the HL-60 assay. The compounds were tested at several concentrations. Figure 7 is a graph showing the inhibitory effects of N-[(l-deoxy-α-L- fucopyranosyl) acetyij-L-proline-L-phenylalanine (#1), N-[(l-deoxy-α-L- fucopyranosyl) acetyl]-L-alanine-L-proline-L-phenylalanine (#2), N- o-t- butoxylcarbonyl-N-α-[(l-deoxy-α-L-fucopyranosyl) acetyl]-L-lysine (#3), N-[4-(l- deoxy-α-L-fucopyranosyl) n-butanoyl]-L-proline-L-phenylalanine (#4), and N-[(l- deoxy-α-L-fucopyranosyl) acetyl]-L-proline-L-phenylglycine (#5) in the Stamper- Woodruff assay. Detailed Description of the Invention As used in this specification and the appended claims, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a glyco-amino acid or glycopeptide" includes mixtures of such compounds, reference to "an ELAM-1" includes reference to mixtures of such molecules, reference to "the formulation" or "the method" includes one or more formulations, methods and/or steps of the type described herein and/or which will become apparent to those persons skilled in the art upon reading this disclosure and so forth. A prodrug is defined as a protected compound wherein the active form of the compound is released within the body of the patient as a result of hydrolysis by enzymes such as esterases. All publications mentioned herein are incorporated by reference. Some standard abbreviations used in connection with the present invention include: BSA, bovine serum albumin; DEAE, diethylaminoethyl; DMSO, dimethyl- sulfoxide; ELAM- 1 , endothelial/leukocyte adhesion molecule- 1 ; HPTLC, high performance thin layer chromatography; LECAM-1, leukocyte/endotheUal cell adhesion molecule- 1; PVC, polyvinylchloride; TLC, thin layer chromatography; TFA, trifluoroacetic acid; Tris, tris (hydroxymethyl) aminomethane; BSA, bovine serum albumin; TBS, tris buffered sakne; DMF, dimethylformamide; Ab-AP, antibody to alkaUne phosphatase; Ac, acetate; Bn, benzyl. Development of the Invention ELAM-1 has a lectin like domain that recognizes sialyl Lewis (sLe x ) tetrasaccharide as shown below in structural formula H The abiUty of SLe x to bind ELAM-1 is described by Lowe et al., £ l (1990) £3:475; Phillips et al., Science (1990) 250:1130; Walz et al., Science (1990) 250:1132; and Tyrell et al., Proc. Natl. Acad. Sci. USA (1991) £&ll0372. It has also been shown (Berg et al., J Biol Chem (1991) 265:14869; Handa et al., Biochem Biophvs Res Commun (1991) 1M:1223) that both ELAM-1, and GMP- 140, also known as P-selectin, recognize the isomeric tetrasaccharide sLe d , as shown below in the structural formula HI. A structural examination of sLe x or sLe a indicates that they share a structural similarity in three dimensional arrangement. Specifically, the siaUc acid and fucose rings are similarly oriented in space in a manner suitable for recognition by the selectins. Amino acids and peptides consist of a carboxyl terminal and an amino terminal. We theorized that we could use a carboxyl terminal of an amino acid or peptide to replace the carboxyUc acid group of siatic acid associated with sLe χ > and to further mimic sLe x - we thought to attach fucose, or an analogue or derivative thereof, at the N- terminal end of an amino acid or peptide. Linking the fucose to an amino acid or peptide tremendously simpUfies the synthesis of these glyco-amino acids or glycopeptides. One face of galactose of sLe x is lipophiUc, and we beUeve this is involved in binding to the selectins. Thus, we further theorized that by replacing the galactose associated with sLe χ ' with a UpophiUc or aromatic amino acid, preferably phenylalanine, diphenylphenylalanine, tyrosine, methoxy-tyrosine, histidine or phenylglycine, we could better mimic sLe χ . We deduced that the corresponding epitopes on the lectin domain of ELAM-1 and perhaps other selectins are spaced in a similar three-dimensional configuration such that attaching fucose, or an analogue or derivative thereof, to an amino acid or a peptide with a free carboxyUc acid group, wherein the amino acid or the peptide preferably has a UpophiUc or an aromatic amino acid, would yield active Ugands that are markedly different from the natural ligand. Following this hypothesis we have designed the simplest form of similar structures which bind to a selectin. This has been done by attaching L-fucose, or an analogue or derivative thereof, using peptide coupling methods to N-terminal amino acids or peptides with a free carboxyUc acid acting as a siaUc acid mimic to provide a series of glyco-amino acids or glycopeptides of structural formula I. This series of glyco-amino acids or glycopeptides is designed to competitively inhibit selectins from binding to their natural ligands. These glyco-amino acids or glycopeptides can be combined with pharmaceutically acceptable excipients to provide pharmaceutical compositions useful in a wide range of treatments. The glyco-amino acids or glycopeptides that contain the appropriate reactive functions can be reacted with suitably protected hydrophobic carriers tike ceramide or a ceramide mimic, steroids, diglycerides or phosphoUpids to form molecules that act as immunomodulators. The glyco-amino acids or glycopeptides of the current invention can act as antagonist ligand molecules, i.e. biochemical blocking agents, by binding to selectins and preventing circulating neutrophils from binding to stimulated endotheUal ceUs, thereby preventing a primary event involved in certain diseases, including the inflammatory response. Agonist ligands have the opposite effect. The synthetic glyco-amino acids or glycopeptides of the present invention are designed to provide a three-dimensionaUy stable configuration for functional groups wherein tigands with fucose, or an analogue or derivative thereof, attached to the N- terminal amino acid or peptide with a free carboxyl group, so as to allow for binding between those groups and receptors on natural selectins. The glyco-amino acids or glycopeptides are represented by the following general structural formula I: wherein m and u are integers of from 1 or 2; p, q and w are integers of from 1 to 6; r and s are integers of from 0 or 1; and t is an integer of from 0 to 3; and A is -COOH or -CH^SO^; B is -Ri, -CH(Ri) 2 , -CH 2 OCH 2 Ri or -CH 2 SCH 2 Ri; D is -Li-[(CH 2 ) w -M] r or -L2-[(CH 2 ) W -M] r ; E is H or -(CH 2 ) w -[K-(CH 2 ) q ] r -M with the proviso that either G is H or M2 is H, when E is -(CH 2 ) w -[K-(CH 2 ) q ] r -Mi ; G is H or -[K-(CH 2 ) q ] r -M 2 with the proviso that either E is H or Mi is H when G is -[K-(CH 2 ) q ] r -M2 ; J is -SO 2 - when D is -Li-[(CH 2 ) W -M] r ; or J is -CO- or -CS- when D is -L2-[(CH 2 ) W -M] r ; K is -O-, -S-, -NH-, -S-S-, -CO-, -CONH- ; Li is -NH-, -CH 2 -, -NHRi 0 r -R 4 with the proviso that Li is either R4 or -NHR when r is 0; L is -O-, -S-, -NH-, -CH 2 -, -OR4, -SR4 , -NHRi 0 r -R4 with the proviso that L2 is either -OR4, -SR4 , -NHR or -R4 when r is 0 ; M, Mi and M2 are independently H or -[CO-OJ s Q is a carrier moiety to obtain multivalent compounds, the carrier moieties selected from the group of amines such as -N(CH 2 CH 2 NH-) 3 , proteins and peptides; X is -R2, -OR2 or -CH 2 OR2; Y is -(CHR 3 ) t - with the proviso that there are no more than two OH groups; or -O-(CHR3) u - with the proviso that there is no more than one OH group ; wherein Ri and R 2 are independently H, an alkyl group containing 1 to 6 carbon atoms, aryl group or an arylalkyl group preferably benzyl; R3 is H or OH; R is an alkyl group containing 1 to 6 carbon atoms, aryl group or an arylalkyl group. Referring now to Figure 1, a cross-sectional view of a blood vessel 1 is shown. The vessel wall 2 is lined internally with endotheUal ceUs 3. The endotheUal ceUs 3 can be activated causing the ceUs 3 to synthesize ELAM-1 which is displayed in Figure 1 as a triangular surface receptor 4. Both red blood ceUs 5 and white blood cells 6 flow in the vessel 1. The white blood cells 6 display carbohydrate ligands 7 which have chemical and physical characteristics which aUow the ligands 7 to bind to the receptors 4. Once the tigand 7 binds to the receptor 4, the white blood ceU 6 is brought through the vessel wall 2 as is shown with the white blood ceU 6A. The white blood ceUs 6B brought into the sμrrounding tissue 8 can have positive effects, such as fighting infection, and negative effects, such as inflammation. An important aspect of the present invention can be described by referring to Figure 2. The glyco-amino acids or glycopeptides of structural formula I are shown as 7 A and can adhere to a selectin such as ELAM-1 by themselves and can be formulated into pharmaceutical compositions, which when administered, wiU effectively block the ELAM-1 and prevent the adhesion of a tigand 7 connected to a white blood cell 6. By administering pharmaceutically effective amounts of the glyco-amino acids or glycopeptides 7A, some, but not all, of the white blood ceUs will not reach the surrounding tissue 8. By slowing the rate at which the white blood ceUs reach the surrounding tissue, inflammation can be prevented and/or alleviated. Another important aspect of the invention can be described with reference to Figure 3. In Figure 3 the LECAM-1 receptor 8 on the white blood cell 6 is blocked by the glyco-amino acids or glycopeptides of formula I represented by 8 A. The present inventors have found that a given glyco-amino acid or glycopeptide, 8 A which presents hydrogen bond donor groups in a configuration as shown in structure I can block E-, L- and/or P-selectins. It is known that for an acute inflammatory response to occur, circulating neutrophils must bind to and penetrate the vascular wall and access the site of injury. Several molecules have been impUcated in this interaction, including a family of putative carbohydrate tigands and their receptors. One molecule that was previously identified is the endogenous carbohydrate tigand for ELAM-1. The present invention provides a family of glyco-amino acids or glycopeptides which bind as the endogenous tigands and thereby block other selectin receptors such as LECAM-1 receptors. The glyco-amino acids or glycopeptides may also be labeled using standard radioactive, fluorescent, enzymic or other label for analytical or diagnostic purposes. We have discovered that in order for a glyco-amino acid or glycopeptide of the invention to bind to a selectin receptor the glycopeptide need not include the identical atoms in the identical configuration as per glyco-amino acids or glycopeptides of structural formula I, but preferably have (1) a stable three dimensional conformation as shown in structure I or (2) a substantially equivalent configuration to that shown in structural formula I. The equivalency of any other Ugand wtil relate to its physical three dimensional structure and the electron configuration of the molecule and in particular the charge and UpophiUcity related characteristics. In order for a glyco-amino acid or glycopeptide of the invention to have a substantiaUy equivalent structure to that shown in structural formula I, the glyco-amino acid or glycopeptide would preferably bind to a selectin receptor when the molecule is aUowed to bind to the receptor under physiological conditions. It has been indicated that "D", "E" or "G" of structural formula I may be a linker which may be attached to any suitable or attachable moiety including a ceramide or a protein or a peptide and is preferably a group with a reactive group thereon which aUows it to covalently bind to a substrate or a pharmaceuticaUy active drug. In one embodiment of the invention the "linker" connects one or more tigands to a support base. The support base is then contacted with a sample to assay for the presence of a desired selectin in the sample. The "tinker" can be used to attach a pharmaceutically effective drug to the glyco- amino acid or glycopeptide at the "D", "G" or "E" position, with the proviso that either G is H or M2 is H when E is -(CH 2 ) w -[K-(CH 2 ) q ] r -Ml and either E is H or Ml is H when G is -[K-(CH 2 ) q ] r -M 2 The (Glyco-amino acid or Glycopeptide-Linker-Drug) conjugate thus formed provides an effective drug delivery system for the linked drug. NSADD or non-steroidal, anti-inflammatory drugs such as naproxen or ibuprofen which act as anti-inflammatory agents could be administered bound to the modified glyco-amino acid or glycopeptide and could be administered systemically in smaUer amounts than usual whtie obtaining an equivalent effect or even greater anti- inflammatory effect at the site of inflammation. Any other drugs which might be attached include, but are not timited to, antibiotics, vasodilators and analgesics. Such a drug delivery system would reduce any systemic effect normally caused by the drug in that the drugs could be administered in amounts of one-half to one-tenth the normal dose and sttil obtain the same anti- inflammatory result at the site of inflammation. Assaying Compounds Of The Invention The glyco-amino acids or glycopeptides can be assayed for their ability to bind to a selectin receptor and/or block the binding site of the receptor and thereby prevent a natural ligand from binding to the selectin receptor. Several assays may be used as described below. ELISA Assay An ELISA assay (Foxall et al, The Journal of Cell Biology (1992) 112:895) is preferably used which consists of the following three steps: 1. 2,3 sLex glycolipid is transferred into microtitre wells as solutions and then evaporated off. Excess, which remained unattached, is washed off with water. The weUs are then blocked with a blocking agent, preferably BSA. 2. Preparation of "multivalent" receptor of the Selectin-IgG chimera is carried out by combining the respective chimera with biotin labelled goat F(ab') 2 anti-human IgG (Fc specific) and streptavidin-alkaline phosphatase diluted appropriately and incubated. This aUows the soluble multivalent receptor complex to form. 3. Potential inhibitors such as glyco-amino acids or glycopeptides of structural formula I are aUowed to react with the soluble receptor. This solution is then placed in the microtitre wells that are prepared in step 1. The plate is incubated to aUow the soluble receptor to bind to its natural ligand. In the presence of a strong inhibitor only a few of the receptors should be free to bind to the microtitre plate coated with the natural ligand. The positive control is the signal produced by the soluble receptor when it is aUowed to react with the natural ligand in the microtitre wells in the absence of any inhibitor. This is considered 100% binding. The signal produced by the receptor that is previously treated with an inhibitor (recorded as O.D.), is divided by the signal produced by the positive control and multiplied by 100 to calculate the % receptor bound to the weU in the presence of the inhibitor. The reciprocal of this is the % inhibition. Identification of Putative ELAM-1 Ligands Using Recombinantly Produced Receptor A complete cDNA for the ELAM-1 receptor was obtttined by PCR starting with total RNA isolated from IL-1 stimulated human umbilical vein endothetium. The resulting cDNA was inserted into the CDM8 plasmid (see Aruffo et al., Proc Natl Acad Sci USA (1987) 84:8573) and the plasmid amptified in E. coti. Plasmid DNA from individual colonies was isolated and used to transfect COS ceUs. Positive plasmids were selected by their abitity to generate COS cells that support HL-60 cell adhesion. DNA sequencing positively identified one of these clones as encoding for ELAM-1 (Bevilacqua et al., Science. (1989) 243:1160; Polte et al., Nucleic Acids Res (1990) 18:1083; Hession et al., Proc Natl Acad Sci USA (1990) 87:1673). These publications are incorporated herein by reference for their disclosure of ELAM-1 and genetic material coding for its production. The complete nucleotide sequence of the ELAM-1 cDNA and predicted amino acid sequence of the ELAM-1 protein are given in the above cited article by Bevilacqua et al., which DNA and amino acid sequences are incorporated herein by reference (see also pubUshed PCT patent appUcation WO90/13300 which was published November 15, 1990, which is incorporated herein by reference). COS cells, expressing membrane-bound ELAM-1, are metaboUcaUy radiolabeled with 3 2PO 4 . These labeled ceUs can be used as probes in two assay systems to screen for recognition of glyco-amino acids or glycopeptides of structural formula I. More specifically, the ligands may be adsorbed to the bottoms of PNC microtiter wells or resolved on TLC plates. In either assay the compounds may be probed for their abitity to support adhesion of ELAM-transfected COS cells, untransfected COS ceUs, or COS ceUs transfected with a plasmid containing an irrelevant cDΝA, under conditions of controUed detachment force (see Swank-Hill et al., Anal Biochem (1987) 183:27: and Blackburn et al., J Biol Chem. (1986) 261:2873 each of which is incorporated herein by reference to disclose the details of such assaying methodology). P-selectin/HL-60 Assay The glyco-amino acids or glycopeptides of structural formula I can be tested for their abitity to inhibit P-selectin binding to its native ligand. A generalized procedure for testing the ligands is given below. A P-selectin/HL-60 assay is preferably used which consists of the foUowing steps: 1. HL-60 ceUs are harvested and pelleted by centrifugation. The cells are washed, counted and the volume adjusted appropriately. 2. PVC microtiter plate is blocked with a blocking agent, and washed with TBS-BSA. 3. P-selectin is diluted appropriately in BSA-TBS Ca containing goat F(ab') 2 anti-human IgG (Fc spec) and streptavidin- alkaline phosphatase. Positive controls have DMF added to equal the highest concentration of DMF in the sample compounds. 4. Ligands are incubated at room temperature with brisk rotation. The tubes are centrifuged to peUet insoluble material. Supernatant from the centrifugation is appUed to quadruplicate wells and ceUs are added. Plate controls are HL-60 ceUs alone, HL-60 ceUs with Ab-AP, P-selectin solution with no ceUs, and the positive test controls described above. The plate is incubated, the cells are peUeted by centrifugation and washed. Para-nitrophenylphosphonate is added to the plate. Color is allowed to develop. Atiqouts from each weU is transferred to a polystyrene microtiter plate and O.D. read at 405 nm. The positive control is the signal produced by the soluble receptor when it is allowed to react with the natural ligand in the absence of any inhibitor. This is considered 100% binding. The signal produced by the receptor that is previously treated with an inhibitor (recorded as O.D.), is divided by the signal produced by the positive control and multiplied by 100 to calculate the % receptor bound to the weU in the presence of the inhibitor. The reciprocal of this is the % inhibition. Stamper- Woodruff Assay (General) Lymphocytes are known to circulate from blood to lymphoid tissues via high endothelial venules (HEV) on lymph nodes. L-selectin is expressed on the surface of lymphocytes and is believed to mediate lymphocyte adhesion by binding to the natural Ugand on the HEN. The glyco-amino acids or glycopeptides of structural formula I can be tested for their abitity to bind to a selectin receptor and/or block the binding site of the receptor and thereby prevent a natural ligand from binding to the selectin receptor. See, for example, Stoolman et al, The Journal of Cell Biology (1983) 9_£:722. The Stamper-Woodruff assay is well known in the art, and generally consists of the foUowing three steps: 1. Preparation of the lymphocytes: (a) The lymphocytes are obtained from the mesenteric nodes of female Swiss Webster mice, by gently teasing tissues with phosphate buffered satine (PBS). The cells are obtained by gently squeezing the cells from the tissues. The ceUs are dispersed and the cell clumps are removed. The single cell suspension is suspended, washed, anil kept on ice until use (less than two hours). Cells are counted and prepared at an appropriate concentration. (b) The superficial and deep cervical lymph nodes of female Sprague-Dawley rats are dissected and prepared in the same way as the mice. 2. Preparation of frozen sections: Superficial or deep cervical lymph nodes are dissected from the animals, snap frozen, and immediately placed in a cryostat for sectioning. 10-μm sections are prepared and transferred onto glass slides, and air dried. 3. Potential inhibitors are added to lymphocyte suspensions 10-30 minutes before the start of the binding assay, and unless otherwise stated, are present throughout the subsequent binding incubation. The frozen sections are used in the order in which they are cut. Aliquots of untreated lymphocytes (positive control), suspensions containing fucoidin (negative control) and suspensions containing potential inhibitors are layered on the sections in an arbitrary sequence such that the control and each test substance are represented once in a series. The binding of the lymphocytes to the HEN is easily distinguishable from binding elsewhere by virtue of the characteristic picture of tightly packed, darkly stained lymphocytes overlaying the histologicaUy distinctive HEN. The number of adherent lymphocytes on each HEV are counted and the average number of adherent cells per HEV (ceUs bound per HEN) is calculated. The results are expressed as a percent of relative binding, wherein the positive control is considered to be 100% binding. One mechanism by which the glyco-amino acids or glycopeptides of the invention could mediate interceUular events would involve the recognition of these glyco-amino acids or glycopeptides on one ceU (e.g., an endothelial cell) by a specific carbohydrate-binding protein (lectin) on an opposing cell (e.g., a leukocyte). Data generated in connection with the present invention indicate that acidic glycolipids isolated from leukocytes and ELAM-1 function as such an oligosaccharide-lectin pair, participating in the interaction of neutrophils with the surface of ceUs of activated vascular endothelium. Many protein-protein interactions have been implicated in neutrophil-endothelium transmigration (see Lo et al, J Immunol (1989) 143:3325: Osborn et al, £eU (1989) 52:1203; Larsen et al, Qsg (1989) 59:305; and Arnaout Blood (1990) 25:1037). While not wishing to be bound to any theory, the present inventors believe it is likely that this lectin-carbohydrate interaction is only one step in a series that result in neutrophil extravasation. The adhesion of selectins to glyco-amino acids or glycopeptides of the invention has been tested. Accordingly, such glyco-amino acids or glycopeptides would be useful in mediating a specific, but possibly weak adhesion that is then stabiUzed and elaborated by the participation of other receptors. Glyco-amino acids or glycopeptides with the structural and functional characteristics described herein, or modifications of these structures, are capable of blocking the interaction of neutrophils with activated vascular endothelium mediated by ELAM-1, and hence provide useful pharmaceutically active agents which can interrupt the adverse effects involved in the interaction of ELAM-1 and circulating neutrophils, e.g., prevent or reduce inflammation. However, the Appticants do not intend to be limited to the above mechanism of action that may account for the prophylactic or therapeutic effects of the glyco-amino acids or glycopeptides of the current invention. Method of Synthesis (General) The glyco-amino acids or glycopeptides of structural formula I can be made using the general synthesis scheme as described below in Scheme I, wherein X is R ORi or CH-^ORi; Y is R 2 or OR 3 ; Ri is H, an alkyl group containing 1 to 6 carbon atoms, aryl group; R 2 is an alkyl group containing 0 to 3 carbon atoms; said alkyl may be substituted with up to 2 OH groups; R 3 is an O-alkyl group containing 1 or 2 carbon atoms; and said O-alkyl may be substituted with 1 OH groups; R 5 , R 6 is a protecting group, preferably acetate or benzyl group; R 7 , Rg is an alkyl or aryl group. In general, as indicated in Scheme I, compound (la) is activated and a protected amino acid (lb), preferably proline, homoprotine, leucine, isoleucine, tyrosine, tryptophan or histidine, is reacted with it to yield (lc). The glycopeptide of the general structure (lc) is deprotected, activated and reacted with another protected amino acid (Id), preferably phenylalanine, 0-benzyl serine, diphenyl-phenylalanine, methoxy tyrosine, bromo-phenylalanine or phenylglycine, to yield (le). The glycopeptide of the general structure (le) is then deprotected to yield (If), a glycopeptide of the structural formula I. Alternatively, la can react with suitably protected peptides, prepared by conventional peptide syntheses, with free amino terminal to provide le. la lc le If U.se and Administration The glyco-amino acids or glycopeptides of structural formula I can be administered to a subject in need thereof to treat the subject by either prophylactically preventing inflammation or relieving it after it has begun. The glyco-amino acids or glycopeptides are preferably administered with a pharmaceuticaUy acceptable carrier, the nature of the carrier differing with the mode of administration, for example, oral administration, usually using a solid carrier and IN. administration a Uquid salt solution carrier. The formulation of choice can be accomptished using a variety of excipients including, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin ceUulose, magnesium carbonate, and the like. Oral compositions may be taken in the form of solutions, suspensions, tablets, pills, capsules, sustained release formulations, or powders. Particularly useful is the administration of the glyco-amino acids or glycopeptides directly in transdermal formulations with permeation enhancers such as DMSO. Other topical formulations can be administered to treat dermal inflammation. A sufficient amount of glyco-amino acids or glycopeptides of the current invention should be administered to bind to a substantial portion of selectin receptors expected to cause or actually causing inflammation so that inflammation can either be prevented or ameliorated. Thus, "treating" as used herein shaU mean preventing or ameUorating inflammation and/or symptoms associated with inflammation. Typically, the compositions of the current invention will contain from less than 1% to about 95% of the active ingredient, preferably about 10% to about 50%. Preferably, between about 10 mg and 50 mg wtil be administered to a child and between about 50 mg and 1000 mg will be administered to an adult. The frequency of administration will be determined by the care given based on patient responsiveness. Other effective dosages can be readily determined by one of ordinary skill in the art through routine trials establishing dose response curves. When determining the dose of glyco-amino acids or glycopeptides of the current invention, which block selectin receptors, to be administered, it must be kept in mind that one may not wish to completely block all of the selectin receptors. In order for a normal heating process to proceed, at least some of the white blood cells or neutrophils must be brought into the tissue in the areas where the wound, infection or disease state is occurring. The amount of glyco-amino acids or glycopeptides of the current invention administered as blocking agents must be adjusted carefully based on the particular needs of the patient while taking into consideration a variety of factors such as the type of disease that is being treated. It is betieved that the glyco-amino acids or glycopeptides of the present invention can be used to treat a wide range of diseases, including diseases such as rheumatoid arthritis, multiple sclerosis and cancer. The compositions of the invention should be applicable to treat any disease state wherein the immune system turns against the body causing the white cells to accumulate in the tissues to the extent that they cause tissue damage, swelling, inflammation and/or pain. The inflammation of rheumatoid arthritis, for example, is created when large numbers of white blood cells quickly enter the joints in the area of disease and attack the surrounding tissues. Formulations of the present invention might also be administered to prevent the undesirable aftereffects of tissue damage resulting from heart attacks. When a heart attack occurs and the patient has been revived, such as by the appUcation of anticoagulants or thrombolytic (e.g., tPA), the endothelial tining where a clot was formed has often suffered damage. When the antithrombotic has removed the clot, the damaged tissue beneath the clot and other damaged tissue in the endothelial lining which has been deprived of oxygen become activated. The activated endothelial ceUs then synthesize the ELAM-1 receptors within hours of the ceUs being damaged. The receptors are extended into the blood vessels where they adhere to the glyco-amino acids or glycopeptides of the current invention on the surface of white blood cells. Large numbers of white blood ceUs are quickly captured and brought into the tissue surrounding the area of activated endotheUal ceUs, resulting in inflammation, sweUing and necrosis which thereby decreases the liketihood of survival of the patient. In addition to treating patients suffering from the trauma resulting from heart attack, patients suffering from actual physical trauma could be treated with formulations of the invention in order to relieve the amount of inflammation and sweUing which normally result after an area of the body is subjected to severe trauma. Other disease states which might be treatable using formulations of the invention include various types of arthritis and adult respiratory distress syndrome. After reading the present disclosure, those skilled in the art will recognize other disease states and/or symptoms which might be treated and/or mitigated by the administration of formulations of the present invention. Other modes of administration wiU also find use with the subject invention. For instance, the glyco-amino acids or glycopeptides of the invention can be formulated in suppositories and, in some cases, aerosol and intranasal compositions. For sup¬ positories, the vehicle composition will include traditional binders and carriers such as, polyalkylene glycols, or triglycerides. Such suppositories may be formed from mixtures containing the active ingredient in the range of about 0.5% to about 10% (w/w), preferably about 1% to about 2%. Intranasal formulations will usually include vehicles that neither cause irritation to the nasal mucosa nor significantly disturb ciliary function. Diluents such as water, aqueous satine or other known substances can be employed with the subject invention. The nasal formulations may also contain preservatives such as, but not limited to, chlorobutanol and benzalkonium chloride. A surfactant may be present to enhance absorption of the subject proteins by the nasal mucosa. The glyco-amino acids or glycopeptides of the invention may also be administered as injectables. TypicaUy, injectable compositions are prepared as liquid solutions or suspensions; solid forms suitable for solution in, or suspension in, liquid vehicles prior to injection may also be prepared. The preparation may also be emulsified or the active ingredient encapsulated in Uposome vehicles. The glyco-amino acids or glycopeptides of structural formula I can be mixed with compatible, pharmaceuticaUy acceptable excipients. Suitable vehicles are, for example, water, saline, dextrose, glycerol, ethanol, or the tike, and combinations thereof. In addition, if desired, the vehicle may contain minor amounts of auxiliary substances such as wetting or emulsifying agents or pH buffering agents. Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in the art. See, e.g. Remington's Pharmaceutical Sci- ences, Mack Publishing Company, Easton, Pennsylvania, 17th edition, 1985. The composition or formulation to be administered wiU, in any event, contain a quantity of the glyco-amino acid or glycopeptide of the invention, adequate to achieve the desired state in the subject being treated. The various glyco-amino acids or glycopeptides of the invention can be used by themselves or in combination with pharmaceuticaUy acceptable excipient materials as described above. However, glyco-amino acids or glycopeptides of the invention can be made as conjugates wherein the glyco-amino acids or glycopeptides are linked in some manner to a label. By forming such conjugates, the glyco-amino acids or glycopeptides of the current invention act as biochemical deUvery systems for the label so that a site of inflammation can be detected. The glyco-amino acids or glycopeptides of the invention could also be used as laboratory probes to test for the presence of a selectin receptor in a sample. Such probes are preferably labeled such as with a radioactive label. There are a number of known labels including radioactive labeled atoms, e.g. radioactive C, O, N, P, or S, fluorescent dyes and enzyme labels which can be attached to the glyco-amino acids or glycopeptides of the invention using known procedures. Labels as well as methods of attaching labels to sugar moieties are disclosed in U.S. patent 4,849,513 issued July 18, 1989 to Smith et al. which patent is incorporated herein by reference to disclose labels and methods of attaching labels. The current invention is shown and described herein in what is considered to be the most practical and preferred embodiments. PubUcations listed herein are incorporated herein by reference to disclose specific procedures on how to make, and/or use the invention. Further, it is recognized that departures may be made therefrom which are within the scope of the invention, and that obvious modifications will occur to one skiUed in the art upon reading this disclosure. EXAMPLES The following examples are provided so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make compounds and compositions of the invention and are not intended to limit the scope of what the inventors regard as their invention. Unless indicated otherwise, parts are parts by weight, temperature is in degrees C, and pressure is at or near atmospheric. EXAMPLE 1 N- |Y 1 -deoxy-α-L-fucopyrano.syDacetyll-L-proline-L-phenyalanine (2f) Method 1 To a stirred mixture of l-aUyl-l-deoxy-2,3,4-tri-0-acetyl-α-L-fucopyranose (2a, 10.0 g , 31.9 mmole, Luengo et al, Tetrahedron Lett. (1992) 23:6911) in a solvent mixture of acetonitrile : carbontetrachloride : water ( 80 ml: 80 ml: 120 ml), 28.0 g (131.2 mmole) of sodium periodate was added, followed by ruthenium trichloride hydrate (145 mg) (Carlsen et al, J. Org. Chem (1981) 4£:3936, Green et al). The reaction became exothermic after 10 minutes and was stirred overnight at room temperature. This mixture was diluted with water (300 ml) and extracted with dichloromethane (2 x 300 ml). The combined organic layer was washed with water (100 ml) and concentrated. The residual oil was dissolved in ethyl acetate (200 ml) and extracted with saturated sodium bicarbonate (30 ml). The organic layer was washed again with water (20 ml) which was combined with the sodium bicarbonate solution extracts. This combined aqueous extract was acidified with 6Ν hydrochloric acid solution to pH 1 and extracted with dichloromethane (2 x 200 ml). The combined organic extracts were washed with water (100 ml), followed by saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to give 6.9 g (20.8 mmole,65%) of (l-deoxy-2,3,4-tri-0-acetyl-α-L-fucopyranosyl)acetic acid (2b) which was used without further purification. A solution of above acid 2b (3.5 g,10.5 mmole) in dichloromethane (20 ml) was mixed with pentafluorophenol trifluoroacetate (1.8 ml, 10.5 mmole) followed by pyridine (0.85 ml, 10.5 mmole) (Green et al, Tetrahedron Letters (1990) 21:5851). This solution was stirred overnight at room temperature, mixed with L-proline benzyl ester hydrochloride (2.3 g, 9.55 mmole) foUowed by diisopropylethylamine (5.76 ml, 33 mmole). This reaction mixture was stirred overnight at room temperature and diluted with ethyl acetate (300 ml). This was washed with 5% potassium hydrogen sulfate solution (50 ml), foUowed by saturated sodium bicarbonate solution (50 ml) and saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to provide the crude benzyl ester 2c. The above crude ester was dissolved in ethyl acetate (100 ml), charged with 10% paUadium on carbon (1.0 g) and stirred overnight under a hydrogen atmosphere (baUoon pressure). This was filtered through celite and the filtrate was extracted with 5% sodium bicarbonate solution (50 ml). The aqueous extract was acidified with 6N hydrochloric acid solution and extracted with ethyl acetate (2 x 100 ml). The combined organic extract was washed with water (50 ml), foUowed by saturated sodium chloride solution (50 ml), dried over sodium sulfate, filtered and concentrated to provide N-[(l-deoxy-2,3,4-tri-0-acetyl-α-L-fucopyranosyl)-acetyl]-L-proline 2d (3.5 g, 8.4 mmole, 80.5%). To a solution of the acid 2d (150 mg, 0.36 mmole) in dichloromethane (1 ml), L-phenylalanine methyl ester hydrochloride (78 mg, 0.36 mmole) was added, followed by benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (188 mg, 0.36 mmole) and dϋsopropylethylamine (0.197 ml, 1.1 mmole) (Coste et al, Tertahadron Letters (1990) 21:205). The mixture was stirred overnight at room temperature and eluted on a sitica gel column (50 ml) with ethyl acetate to provide the protected C-glycodipeptide 2e (180 mg, 0.31 mmole, 85%). A solution of 2e (180 mg, 0.31 mmole) in methanol (2.4 ml) and water (1.2 ml) was added with 2Ν potassium hydroxide solution (1.2 ml). The solution was stirred overnight at room temperature, acidified and evaporated to dryness. The residue was extracted with 2-propanol (3 ml). FUtration and concentration of the 2-propanol extracted provided 2f (60 mg). Method 2 A sample of 2b (1.97 g, 6.16 mmol) was dissolved in dichloromethane (25 ml), N-hydroxysuccimide (ΝHS, 1.0 g, 8.69 mmol) was added to the solution, and the solution was warmed to dissolve the ΝHS. Dicyclohexylcarbodimide (DCC, 1.41 g, 6.83 mmol) was dissolved in dichloromethane (5 ml) and added to the reaction mixture with stirring. After 5 hours, the reaction mixture was cooled to 4° C, filtered and evaporated. The syrupy residue was taken up in ethyl acetate (50 ml), filtered and washed with water (2 x 25 ml). The ethyl acetate layer was dried over anhydrous sodium sulfate, filtered and evaporated. After drying under high vacuum 2.5 g (94%) of an amorphous white solid (l-deoxy-2,3,4-tri-O-acetyl-α-L-fucopyranosyl) acetic acid Ν-hydroxysuccinimide ester (3a) was obtained. A solution of L-proUne-L-phenylalanine (262 mg, 1 mmole) in dimethylformamide (2 ml) was heated with Ν,O-bistrimethylsilylacetamide (0.057 ml) at 800C for 10 minutes. This was added to the N-hydroxylsuccinimide ester 3a (430 mg, 1 mmole). This solution was stirred overnight at room temperature and concentrated. The mixture was eluted on a silica gel column (50 ml, chloroform : methanol : water, 300 :10 : 5) to provide protected C-glycodipeptide 3b (500 mg, 0.87 mmole, 87%) which was hydrolysed in a manner similar to the process described for 2e, to yield 2f. 2b 2a 2d 2c 2e 2f Scheme 3 EXAMPLE 2 N-|Yl-deoxy-α-L-fucopyrano.syl)acetyπ-L-proIine-L-phenylglycine (4b) To a solution of acid 2d (150 mg, 0.36 mmole) in dichloromethane (1 ml), L-phenylglycine methyl ester hydrochloride (78 mg, 0.36 mmole) was added, followed by benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorphosphate (188 mg, 0.36) and dϋsopropylethylamine (0.197 ml, 1.1 mmole). The mixture was stirred overnight and eluted on a sitica gel column (50 ml) with ethyl acetate to provide the protected C-glycodipeptide 4a (180 mg, 0.31 mmole, 85%). A solution of 4a (180 mg, 0.31 mmole) in methanol (2.4 ml) and water (1.2 ml) was mixed with 2Ν potassium hydroxide solution (1.2 ml). The solution was stirred overnight at room temperature, acidified and evaporated to dryness. The residue was extracted with 2-propanol (3 ml). Filtration and concentration of the 2-propanol extracted provided 4b (60 mg). 2d 4a EXAMPLE 3 N-IY 1 -deoxy-α-L-fucopyranosyl)acetyl]-L-alanine- L-proUne-L-phenyalanine(5c) Method 1 A solution of L-alanine-L-proline-L-phenylalanine (5a, 50 mg, 0.15 mmole) in dimethylformamide (0.5 ml) was stirred with N.O-bistrimethylsilylacetamide (75 μl) at 80° C for 5 minutes. This was added to activated ester 3a (65 mg, 0.15 mmole) followed by a catalytic amount of 4-N,N'-dimethylaminopyridine. This mixture was stirred overnight at room temperature and concentrated. The residue was worked up with chloroform and diluted hydrochloric acid solution. The crude protected C-glycotripeptide (5b) was hydrolysed similarly as described in Example 1 to provide 5c (40 mg, 0.076 mmole, 51%). Method 2 A solution of L-alanine-L-proline-L-phenylalanine methyl ester trifluoroacetic acid salt (6a, 2.5 g, 5.4 mmole), prepared from conventional peptide synthesis, and activated ester 3a (3.3 g, 5.4 mmole) in dichloromethane (20 ml) was mixed with dusopropylethylamine (1.0 ml, 5.4 mmole). This mixture was stirred at room temperature for 4 hours and dtiuted with ethyl acetate (300 ml). This combined mixture was washed with 5% potassium hydrogen sulfate (50 ml), foUowed by saturated sodium bicarbonate solution (30 ml), saturated sodium chloride, dried over sodium sulfate, filtered and concentrated. The residue was purified on a sitica gel column (200 ml, dichloromethane : methanol, 92:8) to provide the protected C-glycopeptide 6b (2.4 g, 3.9 mmole, 73%). This sample was hydrolysed in a manner similar to the process described above in Example 1 to yield 5c. Scheme 5 Scheme 6 EXAMPLE 4 N-ω-t-butoxylcarbonyl-N α-| " (l-deoxy- -L-fucopyranosyl)acetyl]- L-lysine (7c) A solution of the activated ester 3a (100 mg, 0.23 mmole) and of N-α-t-butoxycarbonyl-L-lysine (7a, 59 mg, 0.23 mmole) in a 1:1 solvent mixture of water and dimethylforamide (1 ml) was mixed with sodium bicarbonate (100 mg) and stirred overnight at room temperature. The mixture was diluted with ethyl acetate (6 ml) and washed with saturated sodium bicarbonate solution (2 ml). The aqueous layer was separated, washed with another portion of ethyl acetate (2 ml) and acidified with 6Ν hydrochloric acid solution. This was extracted with dichloromethane (6 ml), the organic layer was washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to provide the crude acid 7b (95 mg). The crude acid 7b was hydrolysed in a manner similar to that described in Example 1 to provide 7c (32 mg). Scheme 7 7b 7c EXAMPLE 5 N-[4-(l-deoxy- -L-fucopyranosyl)-n-butanoyl1-L-proline-L-phenylalanine (8g) The aldehyde 8a (2.46 g, 7.78 mmole), obtained by ozone oxidation of 2a, was dissolved in dichloromethane (10 ml) and the ylide t-butyl triphenyl- phosphoranylidene acetate (3.51 g, 9.34 mmole) was added. The reaction was stirred at room temperature for 48 hours and concentrated to dryness. The residue was purified on sitica gel column (20% ethyl acetate in hexane) to give the desired product 8b (2.41 g, 75%) as a colorless oil. The above olefin 8b (2.41 g, 5.83 mmole) was dissolved in methanol (15 ml). A suspension of 10% palladium on carbon (200 mg) in methanol (5 ml) was added to this solution. The reaction was stirred under hydrogen at atmospheric pressure for 28 hrs. The catalyst was removed by filtration through ceUte. Concentration of the filtrate gave the product 8c (2.38 g, 98%) as a colorless oil. The above t-butyl ester 8c (177 mg, 0.43 mmole) was dissolved in dichloromethane (5 ml) and trifluoroacetic acid (0.5 ml) was added to it. The reaction was stirred at room temperature for 2 hrs and concentrated to dryness to give the desired product 8d (154 mg, 100%). A solution of above crude acid 8c (2.2 g, 5.8 mmole) in dichloromethane (10 ml) was added with N-hydroxysuccimide (667 mg, 5.8 mmole) and 1,3- dicyclohexylcarbodimide (5.8 mmole). The mixture was stirred overnight at room temperature and filtered. The solid was rinsed with dichloromethane (5 ml) and the combined filtrates were concentrated to provide the desired activated ester 8e. A mixture of 8e (387 mg, 0.88 mmole) and L-protine-L- phenylalanine (231 mg, 0.88 mmole) in a 1 : 1 solvent mixture of dimethylforamide and water (10 ml) was stirred overnight at room temperature with sodium bicarbonate (370 mg). Base and acid extraction with sodium bicarbonate solution, chloroform and diluted hydrochloric acid provided the acid 8f (130 mg). The above acid 8f was hydrolysed in a manner similar to the process described in Example 1 to provide 8g (60 mg). EXAMPLE 6 N 4-( 1 -deoxy-ct-L-fucopyranosylV n-butanoyl] -L-phenylalanine (9b) A solution of ester 8e (166 mg, 0.36 mmole), L-phenylalanine methyl ester hydrochloride (81 mg, 0.36 mmole) and dϋsopropylethylamine (210 ml, 1.2 mmole) in dichloromethane (2 ml) was stirred overnight at room temperature. The entire mixture was eluted on a sitica gel column (50 ml, ethyl acetate : hexane, 3 : 1) to give the protected ester 9a (160 mg, 85%). Ester 9a was hydrolysed in a manner similarly to the process described in Example 1 to provide 9b. EXAMPLE 7 N-r(l-deoxy-α-L-fucopyranosyl)acetyl]-L-proline D-phenyalanine (10b) To a solution of acid 2d (150 mg, 0.36 mmole) in dichloromethane (1 ml), D-phenylalanine methyl ester hydrochloride (78 mg, 0.36 mmole) was added followed by benzotriazol-1- yloxytripyrroUdinophosphonium hexafluorophsophate (188 mg, 0.36 mmole) and dtisopropylethylamine (0.197 ml, 1.1 mmole). The mixture was stirred overnight at room temperature and eluted on a sitica gel column (50 ml) with ethyl acetate to provide the protected C-glycodipeptide 10a (170 mg). The protected dipeptide 10a was hydrolysed in a manner similarly to the process described in Example 1 to provide 10b. 2a 8d 8e Example 8 l-allyl-l-deoxy-2.3.4-tri-(9-benzyl- -L-fucopyranθ4se (lib) To a solution of 2,3,4-tri-O-benzyl-L-fucopyranose (11a, 10.0 g) in acetonitrile (100 ml) at 0°C, aUyltrimethylsUane (12 ml) was added followed by trimethylsilyltrifluoromethanesulfonate (14.5 ml). The solution was warmed to room temperature and was stirred for 14 hours at room temperature. The mixture was quenched with water (100 ml) in an ice- water bath. The acetonitrile was evaporated in vacuo and the mixture was extracted with ethyl acetate (3 x 100 ml). The combined organic extracts were washed with saturated sodium carbonate solution, foUowed by saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The crude mixture was eluted on a silica gel column (150 ml, hexane : ethyl acetate, 10:1) to provide l-aUyl-l-deoxy-2,3,4-tri-0-benzyl-α-L-fucopyranose (lib, 9.2 g, 79%). Alternatively, in a two step procedure, 2,3,4-tri-O-benzyl-L-fucopyranose (11a, 25 g) was first acetylated with pyridine (25 ml) and acetic anhydride (25 ml) and the crude acetate was dissolved in acetonitrile (150 ml), aUyltrimethylsUane (20 ml) and boron trifluoroetherate (16.5 ml) were added to the solution and the reaction mixture was stirred at room temperature for 14 hours. The reaction was worked up and purified as described above. The crude product (lib) was pure enough for further reactions. Example 9 (l-deoxy-2.3.4-tri-Q-benzyl-oc-L-fucopyranosyl)acetic acid (lie) lib Ue To a stirred mixture of l-a]lyl-l-deoxy-2,3,4-tri-0-benzyl-α-L-fucopyranose (lib, 10.0 g, 31.9 mmole) in a solvent mixture of acetonitrile (80 ml), carbontetrachloride (80 ml) and water (120 ml), sodium periodate (40 g, 8 equivalents) was added, followed by ruthenium trichloride hydrate (1.4 g). The reaction became exothermic after 10 minutes and was stirred overnight at room temperature. This mixture was diluted with water (300 ml), extracted with dichloromethane (3 x 200 ml), and the combined organic layer was washed with water (100 ml) and concentrated. The residual oU was dissolved in ethyl acetate (200 ml) and extracted with saturated sodium bicarbonate( 30 ml). The organic layer was washed again with water (20 ml) which was combined with the sodium bicarbonate solution extracts. This combined aqueous extract was acidified with 6N hydrochloric acid solution to pH 1 and extracted with dichloromethane (2 x 200 ml). The combined organic extracts were washed with water (100 ml), followed by saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to give (1-deoxy- 2,3,4-tri-O-benzyl-α-L- fucopyranosyl) acetic acid (lie, 4.6 g). Example 10 3(l-deoxy-2.3.4-tri-( -benzyl-α-L-fucopyranθ4syl) propionic acid (lid) lib lld A solution of 9-borabicyclo [3.3.1] nonane (9-BBN, 39.3 ml of 0.5 mM) in tetrahydrofuran was added to l-allyl-l-deoxy-2,3,4-tri-0-benzyl-α-L-fucopyranose (lib, 12.0 g) at room temperature. The solution was stirred overnight. IN sodium hydroxide (120 ml) was added very carefuUy foUowed by 30% hydrogen peroxide solution (10 ml) and the reaction mixture was stirred for 3 hours at room temperature. The volatile solvents were removed in vacuo, and the resulting solution was extracted with ethyl acetate (3 x 150 ml). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. The crude mixture was purified on a stiica gel column (200 ml, hexane:ethyl acetate, 1:1) to provide 3(1- deoxy-2,3,4-tri-0-benzyl-α-L-fucopyranosyl)-l-propanol (6.8 g). A solution of the above alcohol (2.5 g) was dissolved in acetone (10 ml), and Jones reagent (6 ml) was added to it at 0° C The mixture was stirred for 3 hours at room temperature and evaporated. The residue was diluted with water (50 ml) and extracted with ethyl acetate (2 x 100 ml). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated to provide 3(l-deoxy- 2,3,4-tri-O-benzyl-α-L-fucopyranosyl) propionic acid (lid, 1.8 g). Example 11 4(l-deoxy-2.3.4-tri-0-acetyl- -L-fucopyranosyl) bύt-2-eneoic acid (llf) Λ r f Ue llf A sample of lie (3.44 g, 8.31 mmoles) was dissolved in dicholoromethane (10 ml) and trifluoroacetic acid (10 ml) was added to it. The solution was stirred at room temperature for 3 hours and concentrated to dryness. The residue was dissolved in ethyl acetate (100 ml) and washed with saturated sodium bicarbonate solution (5 x 10 ml). The aqueous layer was acidified with 6N hydrochloric acid to pH 3 and washed with dichloromethane (3 x 20 ml). The organic extracts were dried over magnesium sulfate, filtered and concentrated to dryness to yield the acid (llf, 100%) as a thick oU which crystallized on standing. Example 12 Sodium (N )-fl-(l-deoxy-α-L-fucopyranosyl) acetyl]-L-Proline- L-phenylalanineol 4sulfate A sample of 2d (310 mg, 0.72 mmoles) was dissolved in tetrahydrofuran (5 ml) and carbonyl diimidazole (CDI, 1174 mg, 0.72 mmoles) was added. The reaction was stirred at room temperature for 1 hour and phenylalanineol (12a, 109 mg, 0.72 mmoles) was added. The reaction was stirred at room temperature for 48 hours after which the reaction was concentrated to dryness. The residue was dissolved in ethyl acetate (30 ml) and washed with IN hydrochloric acid (3 x 10 ml), foUowed by saturated sodium bicarbonate solution (3 x 10 ml) and saturated sodium chloride solution (10 ml). The ethyl acetate layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on sitica gel ( ethyl acetate) to yield (N )-[l-(l-deoxy-α-L-fucopyranosyl) acetyl]-L-proline-L-phenylalanineol (12b, 195 mg, 48%). A mixture of 12b (0.19 g, 0.34 mmol) and sulfur trioxide-pyridine complex (0.19 g, 1.2 mmol) in pyridine (15 ml) was stirred at 55-60° C for 30 minutes. The reaction mixture was cooled, methanol (2 ml) was added and the mixture was stirred for 15 minutes. The reaction mixture was concentrated in vacuo, and purified with silica gel (chloroform : methanol, 9 : 1) to yield 12c (230 mg). 12c was dissolved in methanol (20 ml) and a piece of sodium was added to the solution and the mixture was stirred overnight at room temperature. The mixture was deionised with (H+) cation exchange resin and filtered directly onto (Na+) exchange resin and the mixture was stirred for 40 minutes. The reaction mixture was filtered, dissolved in water and lyophitized to yield 12d (0.135 g). Scheme 12 Example 13 Selectin Binding The glyco-amino acids or glycopeptides of structural formula I can be tested for their abitity to bind to a selectin receptor and/or block the binding site of the receptor and thereby prevent a natural ligand from binding to the selectin receptor (Foxall et al, The Journal of Cell Biology (1992) 117:895). A generalized procedure for testing the ligands is given below. An ELISA assay is preferably used which consisted of the foUowing three steps: 1. 2,3 sLex glycolipid (25 picomol/well) was transferred into microtitre wells as solutions and evaporated off. Excess, which remained unattached, was washed off with water. The weUs were blocked with 5% BSA at room temperature for an hour and washed with PBS containing 1 mM calcium. 2. Preparation of "multivalent" receptor of the Selectin-IgG chimera was carried out by combining the respective chimera (1 μg/mL) with biotin labeUed goat F(ab') 2 anti-human IgG (Fc specific) and streptavidin-alkaline phosphatase diluted 1:1000 in 1% BSA-PBS (1 mM calcium) and incubating at 37°C for 15 min. This aUowed the soluble multivalent receptor complex to form. 3. Potential inhibitors such as glyco-amino acids or glycopeptides of structural formula I were allowed to react with the soluble receptor at 37°C for 45 min. This test assumes that optimal binding, between the soluble phase receptor complex and the inhibitor (non-natural ligand), would occur within this time frame. This solution was placed in the microtitre weUs that were prepared in step 1. The plate was incubated at 37°C for 45 minutes to allow the soluble receptor to bind to its natural ligand. In the presence of a strong inhibitor only a few receptors would be free to bind to the microtitre plate coated with the natural ligand. The positive control was the signal produced by the soluble receptor when it was aUowed to react with the natural Ugand in the microtitre wells in the absence of any inhibitor. This was considered 100% binding. The signal produced by the receptor that was previously treated with an inhibitor (recorded as O.D.), was divided by the signal produced by the positive control and multiplied by 100 to calculate the % receptor bound to the weU in the presence of the inhibitor. The reciprocal of this is the % inhibition. The results shown in figures 4 and 5 indicate that compounds inhibited L- and P-selectin in their ability to bind to their putative natural Ugand. Example 14 P-selectin/HL-60 Assay The glyco-amino acids or glycopeptides of structural formula I can be tested for their abitity to inhibit P-selectin binding to its native ligand. A generalized procedure for testing the ligands is given below. A P-selectin/HL-60 assay is preferably used which consists of the foUowing steps: 1. HL-60 cells were harvested and peUeted by centrifugation. The cells were washed three times with TBS without Ca, counted and the volume adjusted to 1.9xl06/ml in 1% BSA-TBS Ca just prior to use. 2. PVC microtiter plate was blocked with 5% BSA-TBS Ca (ImM) for 1 hour at room temperature. The plate was washed with TBS Ca. 3. P-selectin was diluted to 200 ng/ml in 1% BSA-TBS Ca containing 1:1000 dUutions of goat F(ab') 2 anti-human IgG (Fc spec) and streptavidin-alkatine phosphatase. Positive controls had DMF added to equal the highest concentration of DMF in the sample compounds. 4. Glyco-amino acids or glycopeptides of structure I were incubated at room temperature for an hour on a rotator, with brisk rotation. The tubes were centrifuged to peUet insoluble material. Supernatant from the centrifugation was appUed to quadruplicate wells at 50 μl/well, ceUs were added at 50 μl/weU. Plate controls were HL-60 ceUs alone, HL-60 ceUs with Ab-AP, P-selectin solution with no ceUs and the positive test controls described above. The plate was incubated at 4° C for 1 hour. CeUs were peUeted by centrifugation, washed three times in TBS. Para-nitrophenylphosphonate was added to 1M diethanolamine buffer, pH 9.8, at 1 mg/ml and 75 μl/weU was added to the plate. Color was aUowed to develop for about 45 minutes. 50 μl from each weU was transferred to a polystyrene microtiter plate and O.D. read at 405 nm. Figure 6 has graphs showing the ability of N-[(l-deoxy-α-L-fucopyranosyl) acetyl]-L-proline-L-phenylalanine (#1), and N-[(l-deoxy-α-L-fucopyranosyl) acetyl]- L-alanine-L-proline-L-phenylalanine (#2) to inhibit the binding of sLe to P-selectin. The compounds were tested at several concentrations. Example 15 Stamper- Woodruff Assay Lymphocytes are known to circulate from blood to lymphoid tissues via high endotheUal venules (HEN) on lymph nodes. L-selectin is expressed on the surface of lymphocytes and is believed to mediate lymphocyte adhesion by binding to the natural Ugand on the HEV. The glyco-amino acids or glycopeptides of structural formula I were tested for their ability to bind to a selectin receptor and/or block the binding site of the receptor and thereby prevent a natural Ugand from binding to the selectin receptor. See, for example, Stoolman et al, The Journal of Cell Biology (1983) 96:722. The Stamper-Woodruff assay is well known in the art, and generaUy consists of the foUowing three steps: 1. Preparation of the lymphocytes: (a) The lymphocytes were obtained from the mesenteric nodes of female Swiss Webster mice (23-27 g), by gently teasing tissues by phosphate buffered saline (PBS). Two or three mesenteric lymph nodes from more than two different animals were used. The nodes were put on the well of 6 weU plates and 1 ml of PBS was added. The cells were obtained by gently squeezing the cells from the tissues. The cells were dispersed and the ceU clumps were removed. The single cell suspension was suspended in Hanks balanced solution (BSS) with 0.5 %BSA, washed (2 ml x 3), and kept on ice until use (less than two hours). Cells were counted and prepared at 3-4 x 10 7 cells/ ml. (b) The superficial and deep cervical lymph nodes of female Sprague-Dawley rats (180-200 g) were dissected and prepared in the same way as the mice. Four big lymph nodes (two from each rat) were used for lymphocyte preparation. 2. Preparation of frozen sections: Superficial or deep cervical lymph nodes were dissected from the animals, snap frozen at -70° C (dry ice-acetone), and immediately placed in a cryostat for sectioning (IEC Cryostat at -20° C). 10-μm sections were prepared and transferred onto glass slides. The sections are air dried for 1-2 hours. 3. Potential inhibitors were added to lymphocyte suspensions (1-2 x 10 7 ceUs/ml at 4° C) 10-30 min before the start of the binding assay, and unless otherwise stated, were present throughout the subsequent binding incubation. The binding incubations were conducted on glass slides in 1.4 or 2 cm diameter wax circles. The frozen sections were used in the order in which they are cut. Aliquots of untreated lymphocytes (positive control), suspensions containing fucoidin (100 μg ml, negative control) and suspensions containing potential inhibitors were layered on the sections in an arbitrary sequence such that the control and each test substance were represented once in a series. The series was repeated until a desired number of replicates had been generated. The assay was initiated by layering the 4° C ceU suspension onto the sections (at room temperature). The stides were placed on a metal tray, supported on packed ice, and agitated on a gyratory shaker at 60-100 rpm. The temperature of the slides was equitibrated at 7-10° C. After a 30 minute incubation, the cell suspensions were decanted and the sections were fixed in 3% glutaraldehyde (20 minutes at 4° C). The slides were placed in racks, washed in Dulbecco's phosphate buffered saline (five, one- second immersions), stained with 0.5% toluidine-blue in a 20% ethanol solution (one, 15-60 second immersion), washed in 95% ethanol (one, two-second immersion), and mounted in glycerol. The stides were mounted in emersion-oU and the ceU adhesion was observed under phase contrast microscope briefly at xlOO. The adherent cells were counted on each HEV at x 400. The binding of the lymphocytes to the HEV was easily distinguishable from binding elsewhere by virtue of the characteristic picture of tightly packed, darkly stained lymphocytes overlaying the histologically distinctive HEV. The number of adherent lymphocytes on each HEV were counted on each HEV and the average number of adherent ceUs per HEV (cells bound per HEV) was calculated. The results were expressed as percent of relative binding, wherein the positive control is considered as 100% binding. The results shown in Figure 7 indicate the effect of synthetic glycopeptides {N- [(1-deoxy-α-L-fucopyranosyl) acetyl]-L-proline-L-phenylalanine (#1), N-[(l-deoxy-α- L-fucopyranosyl) acetyl]-L-alanine-L-proline-L-phenylalanine (#2), N-ω-t- butoxylcarbonyl-N- α-[(l-deoxy-α-L-fucopyranosyl) acetyl]-L-lysine (#3), N-[4-(l- deoxy-cc-L-fucopyranosyl) n-butanoyl]-L-proline-L-phenylalanine (#4), N-[(l-deoxy- α-L-fucopyranosyl) acetyl]-L-proUne-L-phenylglycine (#5) and fucoidin} on cell adhesion.

Claims: CLAIMS What is claimed is: 1. A compound comprising the following structural Formula I: wherein m and u are integers of from 1 or 2; p, q and w are integers of from 1 to 6; r and s are integers of from 0 or 1; and t is an integer of from 0 to 3; and A is -COOH or -CH 2 OSO 3 H; B is -Ri, -CH(Ri) 2 , -CH 2 OCH 2 Ri or -CH 2 SCH 2 Ri; D is -Li-[(CH 2 ) w -M] r or -L2-[(CH 2 ) W -M] r ; E is H or -(CH 2 ) w -[K-(CH 2 ) q ] r -Mi with the proviso that either G is H or M2 is H, when E is -(CH 2 ) w -[K-(CH 2 ) q ] r -Mi ; G is H or -[K-(CH 2 ) q ] r -M 2 with the proviso that either E is H or Mi is H when G is -[K-(CH 2 ) q ] r -M2 ; J is -SO 2 - when D is -Li-[(CH 2 ) W -M] r ; or J is -CO- or -CS- when D is -L 2 -[(CH 2 ) W -M] r ; K is -O-, -S-, -NH-, -S-S-, -CO-, -CONH- ; L is -NH-, -CH 2 -, -NHR 0 r -R 4 with the proviso that Li is either R4 or -NHRi when r is 0; L2 is -O-, -S-, -NH-, -CH 2 -, -OR4, -SR4 , -NHR or -R4 with the proviso that L is either -OR4, -SR , -NHRi 0 r -R4 when r is 0 ; M, M 1 and M 2 are independently H or -[CO-Q] s Q is a carrier moiety to obtain multivalent compounds, the carrier moieties selected from the group of amines consisting of -N(CH 2 CH 2 NH-) 3 , proteins and peptides; X is -R2, -OR2 or -CH 2 OR2; Y is -(CHR3) r with the proviso that there are no more than two OH groups; or -O-(CHR3) u - with the proviso that there is no more than one OH group ; wherein Ri and R 2 are independently H, an alkyl group containing 1 to 6 carbon atoms, aryl group or an arylalkyl group; R3 is H or OH; R4 is an alkyl group containing 1 to 6 carbon atoms, aryl group or an arylalkyl group. Z is (d) : 2. The compound of structural formula I of Claim 1 wherein Z is m and u are integers of from 1 or 2; q and w are integers of from 1 to 6; r and s are integers of from 0 or 1; and t is an integer of from 0 to 3; A is -COOH or -CH 2 OSO 3 H; B is -Ri, -CH(Ri) 2 , -CH 2 OCH 2 Ri or -CH 2 SCH 2 Ri; E is H or -(CH 2 ) w -[ -(CH 2 ) q ] r -Mi with the proviso that either G is H or M 2 is H, when E is -(CH 2 ) w -[K-(CH 2 ) q ] r -Mi ; G is H or -[K-(CH 2 ) q ] r -M 2 with the proviso that either E is H or Mi is H when G is -[K-(CH 2 ) q ] r -M2 ; K is -O-, -S-, -NH-, -S-S-, -CO-, -CONH- ; M, Mi and M 2 are independently H or -[CO-Q] s Q is a carrier moiety to obtain multivalent compounds, the carrier moieties selected from the group of amines consisting of -N(CH 2 CH 2 NH-) 3 , proteins and peptides; X is -R2, -OR or -CH 2 OR2; Y is -(CHR3) t - with the proviso that there are no more than two OH groups; or -O-(CHR ) u - with the proviso that there is no more than one OH group ; wherein R 1 and R 2 are independently H, an alkyl group containing 1 to 6 carbon atoms, aryl group or an arylalkyl group; R3 is H or OH. 3. The compound of structural formula I of Claim 1 wherein Z is m and u are integers of from 1 or 2; q and w are integers of from 1 to 6; r and s are integers of from 0 or 1; and t is an integer of from 0 to 3; A is -COOH or -CH 2 OSO 3 H; B is -Ri, -CH(Ri) 2 , -CH 2 OCH 2 Ri or -CH 2 SCH 2 Ri; G is H or -[K-(CH 2 ) q J r -M2 ; K is -O-, -S-, -NH-, -S-S-, -CO-, -CONH- ; M, M and M 2 are independently H or -[CO-Q] s Q is a carrier moiety to obtain multivalent compounds, the carrier moieties selected from the group of amines consisting of -N(CH 2 CH 2 NH-) 3 , proteins and peptides; X is -R2, -OR2 or -CH 2 OR2; Y is -(CHR3) t - with the proviso that there are no more than two OH groups; or -O-(CHR3) u - with the proviso that there is no more than one OH group ; wherein Ri and R 2 are independently H, an alkyl group containing 1 to 6 carbon atoms, aryl group or an arylalkyl group; R3 is H or OH. 4. The compound of structural formula I of Claim 1 wherein Z is u is an integer of from 1 or 2; p and w are integers of from 1 to 6; r and s are integers of from 0 or 1; and t is an integer of from 0 to 3; A is -COOH or -CH 2 OSO 3 H; D is -Li-[(CH 2 ) w -M] r or -L2-[(CH 2 ) W -M] r ; J is -SO 2 - when D is -L -[(CH 2 ) W -M] r ; or J is -CO- or -CS- when D is -L2-[(CH 2 ) W -M] r ; Li is -NH-, -CH 2 -, -NHRi 0 r -R 4 with the proviso that L is either R4 or -NHRi when r is 0; L2 is -O-, -S-, -NH-, -CH 2 -, -OR4, -SR4 , -NHR or -R4 with the proviso that L2 is either -OR4, -SR4 , -NHRi 0 r -R4 when r is 0 ; M is H or -[CO-OJ s Q is a carrier moiety to obtain multivalent compounds, the carrier moieties selected from the group of amines consisting of -N(CH 2 CH 2 NH-) 3 , proteins and peptides; X is -R2, -OR2 or -CH 2 OR2; Y is -(CHR3) t - with the proviso that there are no more than two OH groups; or -O-(CHR3) u - with the proviso that there is no more than one OH group ; wherein R2 is H, an alkyl group containing 1 to 6 carbon atoms, aryl group or an arylalkyl group; R3 is H or OH; R4 is an alkyl group containing 1 to 6 carbon atoms, aryl group or an arylalkyl group. 5. The compound of structural formula I of Claim 1 wherein Z is u is an integer of from 1 or 2; and t is an integer of from 0 to 3; A is -COOH or -CH 2 OSO 3 H; B is -Ri, -CH(Ri) 2 , -CH 2 OCH 2 Ri or -CH 2 SCH 2 Ri; X is -R2, -OR2 or -CH 2 OR2; Y is -(CHR3) t - with the proviso that there are no more than two OH groups; or -O-(CHR3) u - with the proviso that there is no more than one OH group ; Ri and R 2 are independently H, an alkyl group containing 1 to 6 carbon atoms, aryl group or an arylalkyl group; R3 is H or OH. 6. A pharmaceutical composition, comprising a mixture of compounds as claimed in Claim 1 and a pharmaceutically acceptable excipient carrier. 7. A pharmaceutical composition, comprising a mixture of compounds as claimed in Claim 2 and a pharmaceutically acceptable excipient carrier. 8. A pharmaceutical composition, comprising a mixture of compounds as claimed in Claim 3 and a pharmaceutically acceptable excipient carrier. 9. A pharmaceutical composition, comprising a mixture of compounds as claimed in Claim 4 and a pharmaceutically acceptable excipient carrier. 10. A pharmaceutical composition, comprising a mixture of compounds as claimed in Claim 5 and a pharmaceutically acceptable excipient carrier. 11. A method of treatment of a disease in an animal, including a human, comprising administering to said animal a therapeuticaUy effective amount of a compound having the foUowing structural formula I: wherein m and u are integers of from 1 or 2; p, q and w are integers of from 1 to 6; r and s are integers of from 0 or 1; and t is an integer of from 0 to 3; and A is -COOH or -CH^SOsH; B is -Ri, -CH(Ri) 2 , -CH 2 OCH 2 Ri or -CH 2 SCH 2 Ri; D is -Li-[(CH 2 ) W -M] r or -L2-[(CH 2 ) W -M] r ; E is H or -(CH 2 ) w -[K-(CH 2 ) q ] r -Mi with the proviso that either G is H or M 2 is H, when E is -(CH 2 ) w -[K-(CH 2 ) q ] r -Mi ; G is H or -[K-(CH 2 ) q ] r -M 2 with the proviso that either E is H or M 1 is H when G is -[K-(CH 2 ) q ] r -M2 ; J is -SO 2 - when D is -LH(CH 2 ) W -M] r ; or J is -CO- or -CS- when D is -L2-[(CH 2 ) W -M] r ; K is -O-, -S-, -NH-, -S-S-, -CO-, -CONH- ; Li is -NH-, -CH 2 -, -NHRi 0 r -R4 with the proviso that Li is either R4 or -NHRi when r is 0; L2 is -O-, -S-, -NH-, -CH 2 -, -OR4, -SR4 , -NHRi or -R4 with the proviso that L2 is either -OR4, -SR4 , -NHRi 0 r -R4 when r is 0 , M, Mi and M 2 are independently H or -[CO-Q] s Q is a carrier moiety to obtain multivalent compounds, the carrier moieties selected from the group of amines consisting of -N(CH 2 CH 2 NH-) 3 , proteins and peptides; X is -R2, -OR2 or -CH 2 OR2; Y is -(CHR3) r with the proviso that there are no more than two OH groups; or -O-(CHR 3 ) u - with the proviso that there is no more than one OH group ; wherein Ri and R 2 are independently H, an alkyl group containing 1 to 6 carbon atoms, aryl group or an arylalkyl group ; R3 is H or OH; R4 is an alkyl group containing 1 to 6 carbon atoms, aryl group or an arylalkyl group. Zis :CH 2 2)*' HJD (c): -HN s* .N (d) 12. A method of treatment of a disease in an animal, including a human, comprising administering to said animal a therapeuticaUy effective amount of a compound of Claim 2. 13. A method of treatment of a disease in an animal, including a human, comprising administering to said animal a therapeuticaUy effective amount of a compound of Claim 3. 14. A method of treatment of a disease in an animal, including a human, comprising administering to said animal a therapeuticaUy effective amount of a compound of Claim 4. 15. A method of treatment of a disease in an animal, including a human, . comprising administering to said animal a therapeuticaUy effective amount of a compound of Claim 5. 16. The method of Claim 11 wherein the disease is selected from the group consisting of inflammation, autoimmune disease and cancer. 17. The method of Claim 12 wherein the disease is selected from the group consisting of inflammation, autoimmune disease and cancer. 18. The method of Claim 13 wherein the disease is selected from the group consisting of inflammation, autoimmune disease and cancer. 19. The method of Claim 14 wherein the disease is selected from the group consisting of inflammation, autoimmune disease and cancer. 20. The method of Claim 11 wherein the glyco-amino acid or glycopeptide is administered via a route selected from a group consisting of intravenously, orally, transdermaUy and by inhalation. 21. A method of assaying the presence of E, L or P-selectin in a sample comprising the steps of : adhering of a compound of structural formula I to the surface of a substrate; contacting the sample to the substrate surface for a sufficient time to permit said E-, L-, or P-selectin to bind to said compound; and determining the presence of said E-, L- or P-selectin binding to said compound. 22. A method of treating inflammation, comprising the steps of: administering to a patient in need thereof a pharmaceuticaUy effective amount of the composition of Claim 6; monitoring the condition of said patient; and repeating said administration if desired. 23. A method of determining a site of inflammation in a patient, comprising the steps of: administering to a patient a compound of Claim 1 attached to a detectable label; allowing the labeled compound sufficient time to circulate in the patient and locating at the site of inflammation in the patient; and detecting the label and its location in the patient and thereby determining the site of inflammation. 24. The pharmaceutical composition of Claim 6 wherein the compounds are tinked to a "tinker" connected to a pharmaceuticaUy active drug. 25. The pharmaceutical composition of Claim 24 wherein the drug is an anti- inflammatory nonsteroidal drug. 26. A compound of the following structural formula: wherein R9 is Ac or Bn; Rio is H or COOH. 27. A compound of the foUowing structural formula: wherein R 9 is Ac or Bn; and n is an integer of from 1, 2, or 3 28. A compound of the following structural formula: wherein R 9 is Ac or Bn; and n is an integer of from 1, 2, or 3 29. A compound N-[(l-deoxy-α-L-fucopyranosyl)acetyl]-L-proline-L- phenylalanine. 30. A compound N- o-t-butoxylcarbonyl-Ν α-[(l-deoxy-α-L- fucopyranosyl)acetyl]-L-lysine. 31. A compound N-[(l-deoxy-α-L-fucopyranosyl) acetyl]-L-alanine-L- proline-L-phenylalanine. 32. A compound N-[4-(l-deoxy-α-L-fucopyranosyl)-n-butanoyι]-L-protine- L-phenylalanine.

Inventors: ABBAS SAEED ABDALLA, HOLME KEVIN ROSS, LEVY DANIEL EMIL, TANG PENG CHO, ABBAS, SAEED, ABDALLA, HOLME, KEVIN, ROSS, LEVY, DANIEL, EMIL, TANG, PENG, CHO
Applicants: GLYCOMED INC, GLYCOMED INCORPORATED
Application year: 1994
Main classification: C07K1
IPC codes: A61K38, A61P29, A61P35, A61P37, C07D309, C07D405, C07H21, C07K5, C07K9, G01N33